The association between genetic variants of angiopoietin-like 3 and risk of diabetes mellitus is modified by dietary factors in Koreans

Clara Yongjoo Park, Jiyoung Moon, Garam Jo, Juhee Lee, Oh Yoen Kim, Hannah Oh, Hyunjung Lim, Min-Jeong Shin

Research output: Contribution to journalArticle

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Abstract

The role of angiopoietin-like 3 (ANGPTL3) in blood lipid levels, cardiovascular disease risk, and glucose metabolism has received wide attention. This study aimed to examine whether rs11207997 in ANGPTL3 is associated with a 10-year risk of diabetes mellitus (DM) and if the association is modified by the consumption of certain food groups or nutrients. A prospective cohort study was designed using the Ansan–Ansung data of the Korean Genome and Epidemiology Study (n = 7,358; age ≥40 years at baseline). Participants with the T allele of rs11207997, particularly TT homozygotes, had lower triglyceride (TG) and total cholesterol levels than those with CC. There was no association with fasting blood glucose or other biochemical parameters. ANGPTL3 mRNA was positively associated with circulating TG levels and blood pressure (all p < 0.05). Cox proportional hazard models showed that the rs11207997 T allele is associated with a lower risk of DM after adjusting for covariates (hazard ratio: 0.90, 95% confidence interval: 0.812–0.998, p = 0.046). Furthermore, the association between rs11207997 and the risk of DM was modified by dietary factors. These associations were no longer statistically significant when additionally adjusted for baseline TG, a potential mediator. Our data suggest that genetic variation of rs11207997 in the ANGPTL3 gene is associated with risk of DM, possibly through contributing to a lifelong set point of TG.

Original languageEnglish
Article number766
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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Angiopoietins
Diabetes Mellitus
Triglycerides
Alleles
Food
Homozygote
Proportional Hazards Models
Blood Glucose
Fasting
Epidemiology
Cohort Studies
Cardiovascular Diseases
Cholesterol
Genome
Prospective Studies
Confidence Intervals
Blood Pressure
Lipids
Glucose
Messenger RNA

ASJC Scopus subject areas

  • General

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The association between genetic variants of angiopoietin-like 3 and risk of diabetes mellitus is modified by dietary factors in Koreans. / Park, Clara Yongjoo; Moon, Jiyoung; Jo, Garam; Lee, Juhee; Kim, Oh Yoen; Oh, Hannah; Lim, Hyunjung; Shin, Min-Jeong.

In: Scientific Reports, Vol. 9, No. 1, 766, 01.12.2019.

Research output: Contribution to journalArticle

Park, Clara Yongjoo ; Moon, Jiyoung ; Jo, Garam ; Lee, Juhee ; Kim, Oh Yoen ; Oh, Hannah ; Lim, Hyunjung ; Shin, Min-Jeong. / The association between genetic variants of angiopoietin-like 3 and risk of diabetes mellitus is modified by dietary factors in Koreans. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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abstract = "The role of angiopoietin-like 3 (ANGPTL3) in blood lipid levels, cardiovascular disease risk, and glucose metabolism has received wide attention. This study aimed to examine whether rs11207997 in ANGPTL3 is associated with a 10-year risk of diabetes mellitus (DM) and if the association is modified by the consumption of certain food groups or nutrients. A prospective cohort study was designed using the Ansan–Ansung data of the Korean Genome and Epidemiology Study (n = 7,358; age ≥40 years at baseline). Participants with the T allele of rs11207997, particularly TT homozygotes, had lower triglyceride (TG) and total cholesterol levels than those with CC. There was no association with fasting blood glucose or other biochemical parameters. ANGPTL3 mRNA was positively associated with circulating TG levels and blood pressure (all p < 0.05). Cox proportional hazard models showed that the rs11207997 T allele is associated with a lower risk of DM after adjusting for covariates (hazard ratio: 0.90, 95{\%} confidence interval: 0.812–0.998, p = 0.046). Furthermore, the association between rs11207997 and the risk of DM was modified by dietary factors. These associations were no longer statistically significant when additionally adjusted for baseline TG, a potential mediator. Our data suggest that genetic variation of rs11207997 in the ANGPTL3 gene is associated with risk of DM, possibly through contributing to a lifelong set point of TG.",
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